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Can Intraosseous Antibiotics Improve the Results of Irrigation & Debridement and Prosthetic Retention for PJI?

Sponsor
OrthoCarolina Research Institute, Inc. (Other)
Overall Status
Enrolling by invitation
CT.gov ID
NCT03713528
Collaborator
American Association of Hip and Knee Surgeons (Other)
100
Enrollment
10
Locations
1
Arm
64.6
Anticipated Duration (Months)
10
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Purpose of Study: In order to improve upon the variable results seen in irrigation and debridement for periprosthetic infection, we ask if the use of intraosseous regional administration of antibiotics at the time of irrigation and debridement will improve the modest success of standard irrigation and debridement. We will use the existing literature on standard irrigation and debridement procedures to compare with the results of the irrigation and debridement with the use of intraosseous antibiotics.

Impact Question:

How will this study benefit the patient? Currently when an I&D fails, the patient needs to undergo two more major procedures: 1) implant removal and 2) reimplantation of the prosthesis. Any improvement in the results of a standard irrigation and debridement procedure may decrease the number of patients having to go through further extensive procedures to cure their infection.

Condition or Disease Intervention/Treatment Phase
  • Drug: Intraoperative Intraosseous Vancomycin
 Phase 4

Detailed Description

Type of Study:

This is a multicenter, single arm, retrospective/prospective clinical trial.

Treatment Group:

• The treatment group includes any patient with an acute perioperative infection, an acute hematogenous, or a chronic infection with unresectable components and treated with intraoperative intraosseous vancomycin during a one-stage debridement protocol. Additionally, patients will be treated with at least 4 weeks of IV antibiotics under guidance of an infectious disease specialist, and indefinite antibiotic chronic suppression.

Surgical and Antibiotic Administration Technique:

Initially, all patients will receive standard weight based cefazolin (1 gram for patients < 80kg, 2 grams for patients between 80-120kg, and 3 grams for patients over 120kg) preoperatively. Our protocol for MRSA positive patients is to use cefazolin and vancomycin preoperatively. Because irrigation and debridement in patients with gram positive infections are frequently done urgently before exact organism identification and sensitivities are available it is important to cover the patient broadly with cefazolin and vancomycin initially.

The treatment group will receive post debridement intraosseous vancomycin as described below. In total knee infections a pneumatic tourniquet must be used for the procedure. After entering the knee joint the following process is followed:

  1. Fluid is collected in four syringes and placed into two sets of aerobic and anaerobic adult blood culture bottles,

  2. Two synovial tissue cultures from different areas of the joint are obtained and sent for culture,

  3. If not enough fluid is obtained send an additional tissue culture,

  4. Remaining tissue is sent for final pathologic analysis at the end of the case.

After obtaining cultures radical synovial debridement is performed debriding the inner surface of the entire knee capsule including the posterior capsule of the knee. Modular parts will be removed, that is the polyethylene insert for knees.

Debridement and Irrigation Protocol:

After a complete synovectomy is performed along with extraction of modular parts any exposed metallic parts will be scrubbed with a sterile brush soaked in dilute betadine. A 5-step irrigation protocol will then be used for all surgeries:

  1. Pulse lavage with 3 liters of normal saline (NS),

  2. Lavage with 100 cc's of 3% H202 and 100 cc's of sterile water, a 50/50 solution left in wound for 2 minutes,

  3. Lavage 3 liters NS,

  4. Lavage with 1 liter of dilute, sterile Betadine (22.5 ml Betadine/liter NS) - left in wound for 3 minutes

  5. Pulse lavage with 3 liters of NS

After debridement and irrigation the interventional group will receive intraosseous vancomycin 500mg in 150ml of normal saline. This dose was selected based on the studies of Young (10) and Clarke (11) who used this dose in two high risk groups (revision TKA and high BMI patients) with no significant side effects or red man syndromes. This solution will be prepared by the hospital pharmacy and administered via an EZ-IO intraosseous cannula. In total knees the cannula will be placed in the proximal medial tibia using a starter drill slightly smaller than the diameter of the cannula to ensure a press fit just distal to the tibia implant in the vicinity of the pes anserine tendons. 75ccs of the vancomycin solution will be injected as a bolus. Subsequent to this the remaining 75ccs will be placed in the distal femur just proximal to the femoral component evenly split between the medial and lateral femoral condyles.

After irrigation and debridement the wound will be closed over a betadine soaked lap sponge placed between the components. Contaminated drapes and instruments will be removed and the patient will be re-prepped with new drapes. New instruments will be used to insert the new modular parts. After opening the wound and prior to inserting new modular parts the wound will be irrigated this time with the following regime:

  1. Pulse lavage with 3 liters of normal saline (NS),

  2. Lavage with 100 cc's of 3% H202 and 100 cc's of sterile water, a 50/50 solution left in wound for 2 minutes,

  3. Lavage 1 liters NS,

  4. Lavage with 1 liter of dilute, sterile Betadine (22.5 ml Betadine/liter NS) - left in wound for 3 minutes

  5. Pulse lavage with 3 liters of NS

After the modular parts are reinserted the wound is closed with monofilament sutures over drains.

Post-operative treatment will be managed by an infectious disease specialist with at least four weeks of intravenous antibiotics followed by indefinite chronic suppression as recommended by the Musculoskeletal Infection Society (Table 1). Baseline creatinine will be obtained preoperatively and on postop days 1 and 2. Infectious disease consultants will monitor peak and trough levels based on the specific antibiotic administered and they will adjust dosage as indicated.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
100 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Intervention Model Description:
multicenter, single arm, retrospective/prospective clinical trialmulticenter, single arm, retrospective/prospective clinical trial
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Can Intraosseous Antibiotics Improve the Results of Irrigation & Debridement and Prosthetic Retention for PJI?
Actual Study Start Date :
Jan 14, 2020
Anticipated Primary Completion Date :
Jan 1, 2025
Anticipated Study Completion Date :
Jun 1, 2025

Arms and Interventions

Arm Intervention/Treatment
Other: Treatment Group

The treatment group includes any patient with an acute perioperative periprosthetic infection, acute hematogenous infection, or unresectable infection with a gram positive organism sensitive to vancomycin and treated with intraoperative intraosseous vancomycin. Additionally, patients will be treated with at least 4 weeks of IV antibiotics under guidance of an infectious disease specialist, and indefinite antibiotic chronic suppression.

Drug: Intraoperative Intraosseous Vancomycin
After debridement and irrigation the interventional group will receive intraosseous vancomycin 500mg in 150ml of normal saline. This solution will be prepared by the hospital pharmacy and administered via an EZ-IO intraosseous cannula. 75ccs of the vancomycin solution will be injected as a bolus. Subsequent to this the remaining 75ccs will be placed in the distal femur just proximal to the femoral component evenly split between the medial and lateral femoral condyles in knees.
Other Names:
  • Vancomycin

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Recurrence of Infection [1 year]

      The primary outcome measured will be the recurrence of infection by the same organism or reinfection with a new organism as determined by the criteria using the International Consensus Meeting on PJI (1 year follow-up).

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes

    Inclusion Criteria (to be completed at time of consent) I. Acute perioperative periprosthetic infection in the first 90 days following primary surgery OR, II. Acute hematogenous infection with symptoms less than four weeks OR, III. Any patient with a chronic periprosthetic knee infection, or a prosthetic knee that is considered unresectable due to the presence of extremely difficult to extract implants such as cones/sleeves/or long cemented or cementless stems and indicated for an irrigation debridement procedure.

    1. Patients indicated for an irrigation debridement procedure of a knee periprosthetic knee joint infection as defined by the inclusion criteria noted above with a gram positive organism susceptible to vancomycin, defined as:

    1. A sinus communicating with the prosthesis, OR

    2. Two positive cultures obtained from the prosthesis, OR

    3. 3 of 5 criteria:

    1. Elevated ESR (>30mm/hr) and CRP (>10mg/L) ii. Elevated synovial leukocyte count (>3000 cells/µL) or change of ++ on leukocyte esterase strip iii. Elevated synovial neutrophil percentage (>80%) iv. One positive culture v. Positive histological analysis of periprosthetic tissue (>5 neutrophils per high power field in 5 high power fields x400) We understand that on occasion, irrigation & debridement is performed emergently, therefore enrollment may continue without all laboratory/cultures completed. All inclusion criteria in this situation will be confirmed postoperatively.
    1. Any patient >18 years old

    Exclusion Criteria I. Surgical wound that cannot be closed. II. Patients with an acute PJI greater than 90 days following primary surgery (using standard implants).

    1. Hematogenous infection with symptoms greater than four weeks IV. Know hypersensitivity to Vancomycin V. Major Renal disease defined as creatinine > 2.0 (See previous comments, No Red Man syndrome in 2 subsequent studies on intraosseous vancomycin in revision TKA and High BMI patients respectively (9). Additionally, systemic levels were 8 times lower with intraosseous antibiotics than IV Vancomycin.) VI. Unable to use a tourniquet due to vascular disease VII. Pregnant women VIII. Allergy to antibiotic
    Screen Failure (following initial procedure):
    1. Culture negative infections whereby the infecting organism was not identified OR X. Vancomycin-resistant organisms

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of California, San Francisco San Francisco California United States 94143
    2 University of Florida Gainesville Florida United States 32607
    3 Cleveland Clinic Florida Weston Florida United States 33331
    4 Rush University Chicago Illinois United States 60612
    5 University of Nebraska Omaha Nebraska United States 68105
    6 New York University - Langone New York New York United States 10279
    7 Atrium Mercy Hospital Charlotte North Carolina United States 28207
    8 OrthoCarolina Research Institute/OrthoCarolina Charlotte North Carolina United States 28207
    9 Novant Health Charlotte Orthopedic Hospital Charlotte North Carolina United States 28209
    10 University of Utah Salt Lake City Utah United States 84112

    Sponsors and Collaborators

    • OrthoCarolina Research Institute, Inc.
    • American Association of Hip and Knee Surgeons

    Investigators

    • Principal Investigator: Thomas Fehring, MD, OrthoCarolina Research Institute, Inc.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    OrthoCarolina Research Institute, Inc.
    ClinicalTrials.gov Identifier:
    NCT03713528
    Other Study ID Numbers:
    • 9140
    First Posted:
    Oct 19, 2018
    Last Update Posted:
    Apr 1, 2022
    Last Verified:
    Mar 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    No
    Additional relevant MeSH terms:
    Vancomycin

    Study Results

    No Results Posted as of Apr 1, 2022